Asymmetric Synthesis of α-Allyl-α-Aryl α-Amino Acids by Tandem Alkylation/π-Allylation of α-Iminoesters

The first asymmetric synthesis of alpha-allyl-alpha-aryl alpha-amino acids by means of a three-component coupling of alpha-iminoesters, Grignard reagents, and cinnamyl acetate is reported. Notably, the enolate from the tandem process provides a much higher level of reactivity and selectivity than the same enolate generated via direct deprotonation, presumably due to differences in the solvation/aggregation state. A novel method for removal of a homoallylic amine protecting group delivers the free amine congeners. The alpha-allyl group offers a means to generate further valuable alpha-amino acid structures as exemplified by ring closing metathesis to generate a higher ring homologue of alpha-aryl-proline.